Plain English Summary
Trial website
Additional identifiers
EudraCT number
2012-000542-35
ClinicalTrials.gov number
Protocol/serial number
RDD490
Study information
Scientific title
Phase II multicentre study assessing the efficacy of Cabazitaxel in Patients with HER2-negative metastatic breast cancer and having unresectable brain metastases.
Acronym
CiPHER
Study hypothesis
Cabazitaxel is an effective cytotoxic agent that crosses the blood brain barrier and we hope to investigate this attribute in this Phase II study across several UK recruitment centres. Potentially this therapy could afford survival advantage. The primary aim of this study is to assess the feasibility of Cabazitaxel use in breast cancer with brain metastases by determining whether there is evidence for Cabazitaxel increasing 18 week survival from 67% to 81%.
The study will require a maximum of 62 patients. The trial would be terminated for futility if 21 or fewer patients out of the first 31 survive to 18 weeks. Otherwise, the remaining 31 patients will be recruited (unless advised to the contrary by the DMC) and the null hypothesis will be rejected if there are more than 47 survivors at 18 weeks out of the 62 patients.
Ethics approval
NRES Committee North West Liverpool Central, 22/05/2013, REC ref: 13/NW/0153
Study design
Single-arm Phase II study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Patients with HER2-negative metastatic breast cancer and having unresectable brain metastases.
Intervention
Patients on this study will receive Cabazitaxel chemotherapy treatment and palliative radiotherapy will be deferred until evidence of disease progression. These patients will be monitored clinically and radiologically every three and six weeks respectively. Cabazitaxel 25 mg/m2 given on day 1 of each treatment cycle, intravenously, for one hour every 21 days. Diagnostic biopsy of primary tissue, urine samples (baseline and end of treatment) and blood samples (baseline, day 1 of each cycle and at end of treatment) will be collected, processed and stored for future research purposes. This will be with the aim of identifying serum and urinary biomarkers of predictive and prognostic significance. Baseline diagnostic tissues will be used for gene expression profiling and linked with serum and urinary biomarkers and proteomic profiles to identify markers of efficacy, resistance and toxicity.
Intervention type
Drug
Phase
Phase II
Drug names
Cabazitaxel
Primary outcome measure
Overall proportion surviving at 18 weeks from registration
Secondary outcome measures
1. Progression-free survival (PFS) defined as the time from registration to the first of one of the following: development of disease progression or death from any cause
2. Overall response for extracranial visceral metastases (ORv) as defined in RECIST 1.0 , recorded from the start of treatment to 18 weeks
3. Overall response for CNS lesions (ORc) defined as a best response of at least PR, recorded from the start of treatment to 18 weeks
4. Acute toxicity (CTCAE v4) after each treatment cycle up to 18 weeks (for the purposes of safety, toxicity will be assessed up until 28 days after the last dose of study treatment)
5. Time to radiotherapy (measured from treatment start date until commencement of radiotherapy)
6. Time to neurological deterioration
Overall trial start date
01/03/2012
Overall trial end date
05/12/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
First or second line metastatic HER2 negative* breast cancer
1. Oligometastatic brain disease that is unsuitable for surgical resection and/or stereotactic radiosurgery
2. Age 18 years or over
3. ECOG performance status 0-2
4. Diagnosis of metastatic HER2-negative breast cancer
5. At least one measurable target lesion (RECIST 1.0) in the brain** (unsuitable for resection) identified by CT scan or MRI within 21 days of registration.
6. Females of child bearing potential who have a negative pregnancy test prior to study entry
7. Agree to use adequate contraception which they agree to continue for 12 months after the study treatment
8. Ability and capacity to comply with study and follow-up procedure
9. Able to provide written informed consent
*Patients with ER+ve or ER-ve disease are eligible for the study
** Patients with meningeal disease are eligible provided they fit the other criteria. Extracranial disease is not a requirement of this study.
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
62
Participant exclusion criteria
1. Received prior radiotherapy/radiosurgery to the brain (radiotherapy may be offered on disease progression)
2. Received >2 lines of chemotherapy for metastatic recurrent disease (adjuvant treatment is permitted) prior to registration
3. Received any chemotherapy after the diagnosis of brain metastases
4. Previous hormone therapy if it will not be discontinued before Cabazitaxel treatment
5. Patients who have received an increasing dose of steroids to control CNS symptoms within 14 days of registration (steroid use is permitted only when patient is stable at a specific dose at the time of screening)
6. Visceral metastases with no recorded brain metastases
7. Pregnancy or lactation
8. Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 28 days prior to registration
9. Patients with a history of other previous malignancy except treated CIN or non melanomatous skin cancer
10. Grade ≥2 peripheral motor and/or sensory neuropathy
11. Grade ≥2 mucositis oral
12. History of severe hypersensitivity reaction (≥grade 3) to taxanes
13. History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80-containing drugs
14. Other concurrent serious illness or medical conditions which make it undesirable for the patient to enter the trial (including uncontrolled diabetes mellitus)
15. Inadequate organ and bone marrow function as evidenced by:
15.1. Haemoglobin < 9.0 g/dL
15.2. Absolute neutrophil count < 1.5 x 109/L
15.3. Platelet count <100 x 109/L
15.4. AST/SGOT and/or ALT/SGPT >2.5 x ULN
15.5. total bilirubin >1.0 x ULN
15.6. Serum creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded
16. Active infection requiring systemic antibiotic or anti fungal medication.
17. Participation in another clinical trial with any investigational drug within 30 days prior to registration
18. Administration of potent inhibitors and inducers of P450 3A4/5 enzymes within 7 days of registration, or planned concurrent administration whilst on study. This excludes steroid treatment which is standard care treatment for patients with brain metastases
19. Concomitant vaccination with live attenuated vaccines
Recruitment start date
01/03/2012
Recruitment end date
05/12/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
The Clatterbridge Cancer Centre NHS Foundation Trust
Wirral
CH63 4JY
United Kingdom
Funders
Funder type
Industry
Funder name
Sanofi: CABAZ_L_5958
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list